Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis

Abstract

The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using a pheromone, a luteinizing hormone (LH) and/or a human chorionic gonadotrophin (hCG). The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from or suspected of having neurodegenerative diseases or conditions.

1. A method of enhancing neurogenesis in a mammal in need thereof, comprising administering an effective amount of a luteinizing hormone (LH) and erythropoietin (EPO) or a human chorionic gonadotrophin (hCG) and EPO to the mammal, wherein neurogenesis is enhanced in the mammal. 
     
     
       2. The method of  claim 1  wherein the mammal is an adult. 
     
     
       3. The method of  claim 1  wherein the neurogenesis occurs in the subventricular zone. 
     
     
       4. The method of  claim 1  wherein the neurogenesis occurs in the hippocampus. 
     
     
       5. The method of  claim 1  wherein the LH or hCG is administered systemically. 
     
     
       6. The method of  claim 1  wherein the LH or hCG is administered to the brain of the mammal. 
     
     
       7. The method of  claim 1  wherein the mammal has a neurodegenerative disease or condition. 
     
     
       8. The method of  claim 7 , wherein the neurodegenerative disease is a CNS injury. 
     
     
       9. The method of  claim 7 , wherein the neurodegenerative disease is a stroke. 
     
     
       10. The method of  claim 1 , wherein neurogenesis is indicated by the presence of doublecortin-positive or NeuN-positive cells. 
     
     
       11. A method of increasing neural stem cell proliferation in vitro, comprising contacting at least one neural stem cell with an effective amount of a luteinizing hormone (LH) and erythropoietin (EPO) or a human chorionic gonadotrophin (hCG) and EPO. 
     
     
       12. The method of  claim 11  wherein the neural stem cell is derived from an adult mammal. 
     
     
       13. The method of  claim 11  wherein the neural stem cell is derived from the subventricular zone of a mammal. 
     
     
       14. The method of  claim 11  wherein the neural stem cell is derived from the hippocampus of a mammal. 
     
     
       15. A method of enhancing neurogenesis in vitro, comprising contacting at least one neural stem cell with an effective amount of a luteinizing hormone (LH) and erythropoietin (EPO) or a human chorionic gonadotrophin (hCG) and EPO. 
     
     
       16. The method of  claim 15  wherein the neural stem cell is derived from an adult mammal. 
     
     
       17. The method of  claim 15  wherein the neural stem cell is derived from the subventricular zone of a mammal. 
     
     
       18. The method of  claim 15  wherein the neural stem cell is derived from the hippocampus of a mammal.